Matrix metalloproteinase inhibitor delivering devices

Abstract

Devices, systems and methods which employ inhibitors of particular matrix metalloproteinases (MMPs) are provided.

1 . A system for locally delivering one or more agents to a treatment site in or near a heart, the system comprising:
 an implantable device including at least a portion configured to be positioned in the treatment site and to carry and locally deliver one or more inhibitors of one or more matrix metalloproteinases (MMPs) to the treatment site, the one or more MMP inhibitors inhibiting at least one of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1.   
     
     
         2 . The system of  claim 1  wherein the implantable device comprises a lead including a proximal end portion, a distal end portion, an elongate body coupled between the proximal end portion and the distal end portion, and a lumen extending in the elongate body from the proximal end portion to the distal end portion, the lumen configured to deliver the one or more MMP inhibitors. 
     
     
         3 . The system of  claim 1  wherein the implantable device comprises a lead including a proximal end portion, a distal end portion, an elongate body coupled between the proximal end portion and the distal end portion, and a lumen extending in the elongate body from the proximal end portion to the distal end portion, the distal end portion including a coating adapted to carry and deliver the one or more MMP inhibitors. 
     
     
         4 . The system of  claim 1  wherein the implantable device comprises a lead including a proximal end portion, a distal end portion, an elongate body coupled between the proximal end portion and the distal end portion, and a lumen extending in the elongate body from the proximal end portion to the distal end portion, the distal end portion including a drug eluting collar adapted to carry and deliver the one or more MMP inhibitors. 
     
     
         5 . The system of  claim 1  wherein the implantable device comprises a stent including at least one surface portion coated with a material including the one or more MMP inhibitors. 
     
     
         6 . The system of  claim 1  wherein the implantable device comprises a heart patch including at least one surface portion coated with a material including the one or more MMP inhibitors. 
     
     
         7 . The system of  claim 1  wherein the one or more inhibitors are selective inhibitors of at least one of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         8 . The system of  claim 7  wherein the one or more inhibitors are selective inhibitors of at least two of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         9 . The system of  claim 1  wherein the device delivers two or more inhibitors of at least two of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         10 . The system of  claim 1  wherein at least one inhibitor is not a tissue inhibitor of a matrix metalloproteinase (TIMP). 
     
     
         11 . A system for locally delivering one or more agents to a treatment site in or near a heart, the system comprising:
 a percutaneous transluminal catheter including at least a portion configured to be positioned in the treatment site and to carry and locally deliver one or more inhibitors of one or more MMPs to the treatment site, the one or more MMP inhibitors inhibiting at least one of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1.   
     
     
         12 . The system of  claim 11  wherein the percutaneous transluminal catheter comprises a proximal end portion, a distal end portion, an elongate body coupled between the proximal end portion and the distal end portion, and a lumen extending in the elongate body from the proximal end portion to the distal end portion, the lumen configured to deliver the one or more MMP inhibitors. 
     
     
         13 . The system of  claim 11  wherein the percutaneous transluminal catheter comprises a proximal end portion, a distal end portion, and an elongate body coupled between the proximal end portion and the distal end portion, the distal end portion including a coating adapted to carry and deliver the one or more MMP inhibitors. 
     
     
         14 . The system of  claim 11  wherein the percutaneous transluminal catheter comprises a proximal end portion, a distal end portion, and an elongate body coupled between the proximal end portion and the distal end portion, the distal end portion including a drug eluting collar adapted to carry and deliver the one or more MMP inhibitors. 
     
     
         15 . The system of  claim 11  wherein the percutaneous transluminal catheter comprises a proximal end portion, a distal end portion, and an elongate body coupled between the proximal end portion and the distal end portion, the distal end portion including an angioplasty device. 
     
     
         16 . The system of  claim 15  wherein the angioplasty device is adapted to perform at least one of vascular dilatation, stent delivery, brachytherapy, atherectomy, and embolic protection. 
     
     
         17 . The system of  claim 11  wherein the one or more inhibitors are selective inhibitors of at least one of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         18 . The system of  claim 17  wherein the one or more inhibitors are selective inhibitors of at least two MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         19 . The system of  claim 11  wherein the device delivers two or more inhibitors of at two of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         20 . The system of  claim 11  wherein at least one inhibitor is not a tissue inhibitor of a matrix metalloproteinase (TIMP). 
     
     
         21 . A method for treating a myocardial region including at least a portion of an injured area, comprising:
 delivering pacing pulses to the myocardial region of a mammal through one or more electrodes of a plurality of pacing electrodes on a lead; and   delivering one or more inhibitors of one or more MMPs through a lumen in the lead in an amount effective to prevent or inhibit remodeling.   
     
     
         22 . A method for treating a myocardial region including at least a portion of an injured area, comprising:
 delivering pacing pulses to the myocardial region of a mammal through one or more electrodes of a plurality of pacing electrodes on a lead; and   delivering one or more inhibitors of one or more MMPs through a lumen in the lead in an amount effective to enhance pacing.   
     
     
         23 . The method of  claim 21  or  22  wherein the one or more inhibitors inhibit at least one of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         24 . The method of  claim 21  or  22  wherein the one or more inhibitors are selective inhibitors of at least two MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         25 . The method of  claim 20  or  21  wherein the device delivers two or more inhibitors of at least two of MMP-1, MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         26 . The method of  claim 21  or  22  wherein the one or more inhibitors are selective inhibitors of at least one of MMP-2, MMP-8, MMP-13 or MT-1. 
     
     
         27 . The method of  claim 21  or  22  wherein at least one inhibitor is not a TIMP. 
     
     
         28 . A method for treating a myocardial region including at least a portion of an injured area, comprising:
 introducing to a mammal via a catheter a stent which stent is coated with an effective amount of one or more inhibitors of one or more MMPs; and   delivering an effective amount of one or more inhibitors of one or more MMPs via a lumen in the catheter, wherein the inhibitors in the stent may be the same or different than the inhibitors delivered by the catheter.   
     
     
         29 . A method for treating a myocardial region including at least a portion of an injured area, comprising:
 introducing to a mammal a heart patch coated with an effective amount of one or more inhibitors of one or more MMPs.   
     
     
         30 . A system for a heart having a myocardial infarct region, comprising:
 an implantable agent delivery device adapted to carry and release one or more inhibitors of one or more MMPs to a cardiac region including at least a portion of a myocardial infarct region; and   an implantable cardiac rhythm management (CRM) device coupled to the implantable agent delivery device, the implantable CRM device including:
 a pacing circuit to deliver pacing pulses to the cardiac region; and 
 a pacing controller adapted to control the delivery of the pacing pulses, wherein the agent delivery device comprises a pacing lead connected to the implantable CRM device, the pacing lead including at least one electrode to be placed in or near the myocardial infarct region. 
   
     
     
         31 . The system of  claim 24  wherein the pacing lead comprises the implantable agent delivery device. 
     
     
         32 . The system of  claim 31  wherein the pacing lead comprises a proximal end portion connected to the implantable CRM device and a distal end portion configured to be placed in or near the myocardial infarct region, the distal end portion including a coating adapted to carry and deliver the one or more inhibitors. 
     
     
         33 . The system of  claim 31  wherein the pacing lead comprises a proximal end portion connected to the implantable CRM device and a distal end portion configured to be placed in or near the myocardial infarct region, the distal end portion including a drug eluting collar adapted to carry and deliver the one or more inhibitors. 
     
     
         34 . A system to treat a myocardial infarct, comprising:
 an implantable agent delivery device adapted to contain one or more inhibitors of one or more MMPs and to release the one or more inhibitors to a cardiac region including at least a portion of a myocardial infarct region, wherein the device includes a stent; and   a catheter having a lumen adapted for delivery of one or more inhibitors of one or more MMPs.